1. Field of the Invention
This invention relates to a system for coating a tubular implantable medical device, such as a stent, and a method of coating a device using the system.
2. Description of the Background
Blood vessel occlusions are commonly treated by mechanically enhancing blood flow in the affected vessels, such as by employing a tubular implantable medical device known as a stent. Stents act as scaffoldings, functioning to physically hold open and, if desired, to expand the wall of the passageway. Stents are capable of being compressed, so that they can be inserted through small lumens via catheters, and then expanded to a larger diameter once they are at the desired location.
FIG. 1 illustrates a conventional stent 10 formed from a plurality of structural elements including struts 12 and connecting elements 14. The plurality of struts 12 are radially expandable and interconnected by connecting elements 14 that are disposed between adjacent struts 12, leaving lateral openings or gaps 16 between adjacent struts 12. Struts 12 and connecting elements 14 define a tubular stent body having an outer, tissue-contacting surface and an inner surface.
Stents are used not only for mechanical intervention but also as vehicles for providing biological therapy. Biological therapy can be achieved by medicating the stents. Medicated stents provide for the local administration of a therapeutic substance at the diseased site. Local delivery of a therapeutic substance is a preferred method of treatment because the substance is concentrated at a specific site and thus smaller total levels of medication can be administered in comparison to systemic dosages that can produce adverse or even toxic side effects for the patient.
One method of medicating a stent involves the use of a polymeric carrier coated onto the surface of the stent. A composition including a solvent, a polymer dissolved in the solvent, and a therapeutic substance dispersed in the blend is applied to the stent by immersing the stent in the composition or by spraying the composition onto the stent. The solvent is allowed to evaporate, leaving on the stent surfaces a coating of the polymer and the therapeutic substance impregnated in the polymer.
As noted above, one of the methods of applying a drug composition to a stent involves spraying the composition onto the stent. The composition can be atomized to produce small droplets. Atomization is used because the droplet size can be made smaller than the size of the stent's structural elements, thus enabling a substantially conformal coating. However, there are potential shortcomings associated with a spray coating process. For instance, many of the drugs and polymers that are applied to stents are toxic when inhaled by humans. As the polymeric drug solutions are atomized, therefore, great care must be taken to avoid occupational exposure to the personnel conducting the process. Hoods, glove boxes, enclosures, and shrouds can be used to prevent toxic aerosol inhalation, but at a cost of decreased efficiency and increased expenditures on equipment. In light of these safety and manufacturing concerns, a stent coating method that avoids atomization of the coating can be advantageous.
Another disadvantage of a spray coating process is that the transfer efficiency can be comparatively low. Only droplets which fall onto the stent's structural elements are incorporated into the coating. If the spray pattern is larger than the stent, much of the spray can be wasted. Moreover, the stent's body can have a number of open spaces or gaps between the structural elements that allow the spray to pass through, and therefore be unused. The components of the coating compositions can be very expensive. For instance, many of the drugs applied to stents are small molecule agents or biologically derived substances such as peptides and gene therapy agents that are very costly. A stent coating method which transfers the coating solution in a more direct manner to the stent structure would therefore have a manufacturing cost advantage.
Yet another shortcoming of a spray coating process is that it can be difficult to direct the coating composition to a selected stent surface such as only onto the outer surface of the stent. The outer or tissue-contacting surface of the stent is the surface that is pressed against the vessel wall. Drug released from the outer surface of the stent is mostly diffused into the tissue, thereby maximizing the local delivery of the drug. Drug present on the inner or lumen contacting surface of the stent, on the other hand, can diffuse into the blood stream where it is transported by the blood flow to an area away from the site of stent implantation. For particular drugs, it may be advantageous to have a stent where the coating is only present on the outer surface of the stent. For example, certain drugs can produce adverse or even toxic side effects for the patient when they are released into the blood stream and carried into the vascular system. By having a drug coating limited to the outer surface of the stent, one can minimize the amount of these types of drugs that are delivered outside of the treatment area.
There are other reasons to produce a stent that only has the drug coating on the outer surface of the stent. In manufacturing drug eluting stents, one of the goals of the manufacturing process is to minimize the contribution of the coating to the stent dimensions (i.e., to minimize the thickness of the coating). By minimizing the thickness, or profile, of the stent's structural members, one can achieve better maneuverability as the stent is delivered to the site of implantation. Furthermore, because foreign materials in the body can elicit a chronic foreign body response, it is desirable to minimize the amount of polymer applied to the stent body. By applying the polymeric drug coating to only the outer surface of the stent, the amount of polymer exposed to the body of the patient can be reduced.
Spray or dip coating processes coat both the inner and outer surfaces of the stent. Masking techniques can be used to limit the coating application to the inner or outer surface. For example, a mandrel can be inserted through the longitudinal bore of the stent to mask the inner surface such that the coating is deposited only on the outer surface. It may be, however, desirable to coat the inner surface of the stent with a first type of drug, such as an angiogenic drug, and the outer surface with a second type of a drug such as one used for the treatment of restenosis. If the inner surface of the stent is first masked for the deposition of a coating on the outer surface of the strut, masking the coated outer surface of the stent to form a coating on the inner surface of the stent may cause damage to the coating on the outer surface. Accordingly, a shortcoming of the conventional coating techniques is the inability of manufacturers to coat the inner and outer surfaces of the stent with different pharmaceutical agents.
Another shortcoming of the above-described method of medicating a stent is the potential for coating defects. While some coating defects can be minimized by adjusting the coating parameters, other defects occur due to the nature of the application process. For example, during a spray coating process, a stent is commonly supported by a mandrel. Because the spray applicator sprays the entire surface of a stent as the composition is applied, and because there is a high degree of surface contact between the stent and the mandrel, there can be stent regions in which the liquid composition can flow, wick, and collect. Upon the removal of the coated stent from the mandrel, the excess coating may stick to the mandrel, thereby removing some of the coating from the stent in the form of peels as shown in FIG. 2, or leaving bare areas as shown in FIG. 3. Alternatively, as illustrated in FIG. 4, the excess coating may stick to the stent, thereby leaving excess coating as clumps or pools on the struts or webbing between the struts. These types of defects can cause adverse biological responses after the coated stent is implanted into a biological lumen. For instance, the tissue surrounding the biological lumen adjacent to the ends of stent 10 can adversely react to the coating defects (known as the “edge effect.”)
Accordingly, the present invention provides a system and method for coating a tubular implantable medical device that addresses these needs.